Characterization of apolipoprotein A-I peptide phospholipid interaction and its effect on HDL nanodisc assembly

Hiren Patel,1 Bei Ding,2 Kelsey Ernst,3 Lei Shen,2 Wenmin Yuan,3 Jie Tang,3 Lindsey R Drake,1 Jukyung Kang,3 Yaoxin Li,2 Zhan Chen,2 Anna Schwendeman1,3,41Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA; 2Department of Chemistry, University of Michi...

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Autores principales:	Patel H, Ding B, Ernst K, Shen L, Yuan W, Tang J, Drake LR, Kang J, Li Y, Chen Z, Schwendeman A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	apoA-1 mimetic peptide HDL high density lipoprotein LUV large unilamellar vesicle SFG sum frequency generation DLS dynamic light scattering TEM transmission electron microscopy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f351c2d63f7849a9af05bf71554f6b32
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spelling	oai:doaj.org-article:f351c2d63f7849a9af05bf71554f6b322021-12-02T04:16:36ZCharacterization of apolipoprotein A-I peptide phospholipid interaction and its effect on HDL nanodisc assembly1178-2013https://doaj.org/article/f351c2d63f7849a9af05bf71554f6b322019-04-01T00:00:00Zhttps://www.dovepress.com/characterization-of-apolipoprotein-a-i-peptide-phospholipid-interactio-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hiren Patel,1 Bei Ding,2 Kelsey Ernst,3 Lei Shen,2 Wenmin Yuan,3 Jie Tang,3 Lindsey R Drake,1 Jukyung Kang,3 Yaoxin Li,2 Zhan Chen,2 Anna Schwendeman1,3,41Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA; 2Department of Chemistry, University of Michigan, Ann Arbor, MI, USA; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA; 4Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USABackground: Synthetic HDLs (sHDLs), small nanodiscs of apolipoprotein mimetic peptides surrounding lipid bilayers, were developed clinically for atheroma regression in cardiovascular patients. Formation of HDL involves interaction of apolipoprotein A-I (ApoA-I) with phospholipid bilayers and assembly into lipid-protein nanodiscs.Purpose: The objective of this study is to improve understanding of physico-chemical aspects of HDL biogenesis such as the thermodynamics of ApoA-I-peptide membrane insertion, lipid binding, and HDL self-assembly to improve our ability to form homogeneous sHDL nanodiscs that are suitable for clinical administration.Methods: The ApoA-I-mimetic peptide, 22A, was combined with either egg sphingomyelin (eSM) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) phospholipid vesicles to form sHDL. The sHDL assembly process was investigated through lipid vehicle solubilization assays and characterization of purity, size, and morphology of resulting nanoparticles via gel permeation chromatography (GPC), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Peptide-lipid interactions involved were further probed by sum frequency generation (SFG) vibrational spectroscopy and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). The pharmacokinetics of eSM-sHDL and POPC-sHDL nanodiscs were investigated in Sprague Dawley rats.Results: sHDL formation was temperature-dependent, with spontaneous formation of sHDL nanoparticles occurring only at temperatures exceeding lipid transition temperatures as evidenced by DLS, GPC, and TEM characterization. SFG and ATR-FTIR spectroscopy findings support a change in peptide-lipid bilayer interactions at temperatures above the lipid transition temperature. Lipid-22A interactions were stronger with eSM than with POPC, which resulted in the formation of more homogeneous sHDL nanoparticles with longer in vivo circulation time as evidenced the PK study.Conclusion: Physico-chemical characteristics of sHDL are in part determined by phospholipid composition. Optimization of phospholipid composition may be utilized to improve the stability and homogeneity of sHDL.Keywords: apoA-1 mimetic peptide, high-density lipoprotein (HDL), large unilamellar vesicle (LUV), sum frequency generation (SFG), dynamic light scattering (DLS), transmission electron microscopy (TEM)Patel HDing BErnst KShen LYuan WTang JDrake LRKang JLi YChen ZSchwendeman ADove Medical PressarticleapoA-1 mimetic peptideHDLhigh density lipoproteinLUVlarge unilamellar vesicleSFGsum frequency generationDLSdynamic light scatteringTEMtransmission electron microscopyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 3069-3086 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	apoA-1 mimetic peptide HDL high density lipoprotein LUV large unilamellar vesicle SFG sum frequency generation DLS dynamic light scattering TEM transmission electron microscopy Medicine (General) R5-920
spellingShingle	apoA-1 mimetic peptide HDL high density lipoprotein LUV large unilamellar vesicle SFG sum frequency generation DLS dynamic light scattering TEM transmission electron microscopy Medicine (General) R5-920 Patel H Ding B Ernst K Shen L Yuan W Tang J Drake LR Kang J Li Y Chen Z Schwendeman A Characterization of apolipoprotein A-I peptide phospholipid interaction and its effect on HDL nanodisc assembly
description	Hiren Patel,1 Bei Ding,2 Kelsey Ernst,3 Lei Shen,2 Wenmin Yuan,3 Jie Tang,3 Lindsey R Drake,1 Jukyung Kang,3 Yaoxin Li,2 Zhan Chen,2 Anna Schwendeman1,3,41Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA; 2Department of Chemistry, University of Michigan, Ann Arbor, MI, USA; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA; 4Biointerfaces Institute, University of Michigan, Ann Arbor, MI, USABackground: Synthetic HDLs (sHDLs), small nanodiscs of apolipoprotein mimetic peptides surrounding lipid bilayers, were developed clinically for atheroma regression in cardiovascular patients. Formation of HDL involves interaction of apolipoprotein A-I (ApoA-I) with phospholipid bilayers and assembly into lipid-protein nanodiscs.Purpose: The objective of this study is to improve understanding of physico-chemical aspects of HDL biogenesis such as the thermodynamics of ApoA-I-peptide membrane insertion, lipid binding, and HDL self-assembly to improve our ability to form homogeneous sHDL nanodiscs that are suitable for clinical administration.Methods: The ApoA-I-mimetic peptide, 22A, was combined with either egg sphingomyelin (eSM) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) phospholipid vesicles to form sHDL. The sHDL assembly process was investigated through lipid vehicle solubilization assays and characterization of purity, size, and morphology of resulting nanoparticles via gel permeation chromatography (GPC), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Peptide-lipid interactions involved were further probed by sum frequency generation (SFG) vibrational spectroscopy and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). The pharmacokinetics of eSM-sHDL and POPC-sHDL nanodiscs were investigated in Sprague Dawley rats.Results: sHDL formation was temperature-dependent, with spontaneous formation of sHDL nanoparticles occurring only at temperatures exceeding lipid transition temperatures as evidenced by DLS, GPC, and TEM characterization. SFG and ATR-FTIR spectroscopy findings support a change in peptide-lipid bilayer interactions at temperatures above the lipid transition temperature. Lipid-22A interactions were stronger with eSM than with POPC, which resulted in the formation of more homogeneous sHDL nanoparticles with longer in vivo circulation time as evidenced the PK study.Conclusion: Physico-chemical characteristics of sHDL are in part determined by phospholipid composition. Optimization of phospholipid composition may be utilized to improve the stability and homogeneity of sHDL.Keywords: apoA-1 mimetic peptide, high-density lipoprotein (HDL), large unilamellar vesicle (LUV), sum frequency generation (SFG), dynamic light scattering (DLS), transmission electron microscopy (TEM)
format	article
author	Patel H Ding B Ernst K Shen L Yuan W Tang J Drake LR Kang J Li Y Chen Z Schwendeman A
author_facet	Patel H Ding B Ernst K Shen L Yuan W Tang J Drake LR Kang J Li Y Chen Z Schwendeman A
author_sort	Patel H
title	Characterization of apolipoprotein A-I peptide phospholipid interaction and its effect on HDL nanodisc assembly
title_short	Characterization of apolipoprotein A-I peptide phospholipid interaction and its effect on HDL nanodisc assembly
title_full	Characterization of apolipoprotein A-I peptide phospholipid interaction and its effect on HDL nanodisc assembly
title_fullStr	Characterization of apolipoprotein A-I peptide phospholipid interaction and its effect on HDL nanodisc assembly
title_full_unstemmed	Characterization of apolipoprotein A-I peptide phospholipid interaction and its effect on HDL nanodisc assembly
title_sort	characterization of apolipoprotein a-i peptide phospholipid interaction and its effect on hdl nanodisc assembly
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/f351c2d63f7849a9af05bf71554f6b32
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Characterization of apolipoprotein A-I peptide phospholipid interaction and its effect on HDL nanodisc assembly

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